EFFECT OF AMILORIDE ON ISCHEMIA AND REPERFUSION INJURY IN ISOLATED, PERFUSED RAT HEARTS

The effect of amiloride, a potent inhibitor of Na+/H+ exchange, on isc haemic reperfused rat hearts was studied in order to investigate wheth er Na+/H+ exchange or Na+/Ca2+ exchange is involved in ischaemia-reper fusion injury, When hearts were pre-ischaemically loaded with 100 mu M amiloride, recovery of left ventricular developed pressure was signif icantly better than in control hearts, whereas recovery of heart rate at 30-min reperfusion was unaffected. Amiloride pretreatment also decr eased creatine phosphokinase activity in the coronary effluent and com pletely abolished occurrence of ventricular arrhythmias during reperfu sion. It also inhibited intracellular Na+ accumulation early in reperf usion (within 5 min), whereas in the late stage (from 5 to 30 min), Ca 2+ overload was inhibited. The findings suggest that Na+/H+ exchange p articipates mainly in the early stage of reperfusion injury and the Na +/Ca2+ exchange system, secondary to Na+/H+ exchange, in the late stag e. The reduction in postischaemic cardiac dysfunction induced by amilo ride pretreatment may be attributable to inhibition of the resultant C a2+. accumulation during reperfusion.